Described herein is a composition and process for synthesizing a hemoglobin-based oxygen carrier (HBOC) composition that includes a polymerized hemoglobin locked in at least one of the tense or relaxed quaternary state and has a molecular weight of at least about 500 kDa. The PolyHb may have a cross-linker to hemoglobin molar ratio of at least about 20:1. The polymerized hemoglobin is useful for delivering oxygen to cells, such as for treatment of anemic conditions in a subject, perfusion of tissues or organs, and supplementing cell culture media in cell culturing systems.